Title |
A sequence-specific threading tetra-intercalator with an extremely slow dissociation rate constant
|
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Published in |
Nature Chemistry, September 2011
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DOI | 10.1038/nchem.1151 |
Pubmed ID | |
Authors |
Garen G. Holman, Maha Zewail-Foote, Amy Rhoden Smith, Kenneth A. Johnson, Brent L. Iverson |
Abstract |
A long-lived and sequence-specific ligand-DNA complex would make possible the modulation of biological processes for extended periods. For this purpose, we are investigating a polyintercalation approach to DNA recognition in which flexible chains of aromatic units thread back and forth repeatedly through the double helix. Here we describe the DNA-binding behaviour of a threading tetra-intercalator. Specific binding was observed on a relatively long DNA strand that strongly favoured a predicted 14 base-pair sequence. Kinetic studies revealed a multistep association process, with sequence specificity that primarily derives from large differences in dissociation rates. The rate-limiting dissociation rate constant of the tetra-intercalator complex dissociating from its preferred binding site was extremely slow, corresponding to a half-life of 16 days. This is one of the longest non-covalent complex half-lives yet reported and, to the best of our knowledge, the longest for a DNA-binding molecule. |
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Other | 8 | 14% |
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Neuroscience | 1 | 2% |
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